Abstract
Isoginkgetin (ISOGK) is a bioactive biflavonoid isolated from Ginkgo biloba , an eminent Chinese herbal medicine with hypolipidemic properties. This study was designed to investigate the therapeutic effects and mechanisms of action of ISOGK in treating hypercholesterolemia and atherosclerosis. Compared with vehicle-treated ApoE -/- mice, ISOGK-treated mice showed a reduction in the plaque area of the aorta and the sinus, regardless of gender. Treatment with ISOGK also reduced serum and hepatic lipid levels. Surface Plasmon Resonance and Cellular Thermal Shift Assay assays discovered that ACLY can directly bind to ISOGK, identifying ACLY as a direct target of ISOGK. Further Molecular Docking and ADP-Glo Kinase Assay confirmed that ISOGK can bind to ACLY and inhibit its enzyme activity. Finally, the lipid-lowering and anti-atherosclerotic effects of ISOGK were abolished by hepatic knockdown of ACLY via treatment with GalNAc-siACLY. The present study identified ISOGK as an effective bioactive molecule that limits hypercholesterolemia and atherosclerosis by pharmacological inhibition of ACLY.
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